There are 2 common methods for creating a transgenic animal the first is microinjection and the second is gene knockouts.
Mircoinjection only has a 2% sucess rate and 99.9% of the trasngenic results arise due to random intergration not homologous recombination. This methos is not appropriate for generating null replacements.
The gene knockout method involves cloning the gene you wish to knockout; inserting a selectoin marker i.e. an antibiotic resistance gene; introducing the mutated gene into the embryonic cells and then selecting for a homologous recombinant .